Search

Atrial natriuretic peptide (CDD/ANP-99-126) has been identified as a bronchodilator in various species including humans. We investigated the effect of urodilatin (CDD/ANP-95-126) in 18 clinically stable asthmatics showing an increase of the FEV1 by > or = 15% after salbutamol inhalation. Prior to the study inhaled beta 2-agonists were withheld for 8 h. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25), blood pressure, and heart rate in intravenous infusion of 20, 40 or 60 ng kg-1 min-1 urodilatin was administered for 40 min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of 1.25 mg salbutamol. Forty and 60 ng kg-1 min-1 urodilatin showed a significant effect on the central (FEV1, PEF, MEF75) and peripheral airways (MEF50, MEF25) after 10 min infusion (P < 0.05). A bronchodilation not significantly different from 1.25 mg salbutamol was induced by 40 ng kg-1 min-1 in the central airways only, while 60 ng kg-1 min-1 led to a similar effect at all levels of the bronchial tree. Lung function parameters returned to baseline within 30 min after cessation of the urodilatin infusion. Heart rate showed a tendency to increase after 40 min infusion (P < 0.05), but blood pressure did not change significantly. In conclusion, the maximal bronchodilating effect of intravenous urodilatin in clinically stable asthmatics was comparable to 1.25 mg salbutamol.

A pilot study was performed in patients after liver transplantation (Ltx) to examine the effect of continuous intravenous urodilatin (URO, CDD/ANP-95-126)-infusion as an alternative therapy of acute renal failure (ARF) resistant to conventional therapy. Eight patients who developed ARF after liver transplantation and fulfilled requirements for haemodialysis/haemofiltration were treated. After URO infusion was started, renal function improved and all patients developed a strong diuresis and natriuresis within 2-4 h. The extracellular expansion due to sodium and water retention in anuric/oliguric ARF lead to an increased central venous pressure (CVP) and elevated blood pressure. During the URO infusion CVP declined and systolic, as well as diastolic, blood pressure were stable. In six patients where haemodialysis/haemofiltration could be avoided, serum creatinine (SC) and blood urea nitrogen (BUN) declined during URO treatment and creatinine clearance (CC) also improved significantly. Fluid and electrolyte disturbances changed promptly and normalized. This was in concordance with renal excretion of electrolytes. Two patients still required haemodialysis/haemofiltration. The six patients who did not require haemodialysis/haemofiltration after URO treatment normalized concerning their renal function and did well in a control period of 12 weeks. The study shows that continuous low dose URO infusion may present a new concept for treatment of postoperative acute renal failure resistant to conventional therapy.

Urodilatin (ANF(95-126)), an analogue of the atrial natriuretic factor (ANF(99-126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1 +/- 0.8 years; X +/- SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 micrograms kg-1 body weight (bw) (n = 6 per dosage group). Urodilatin dose-dependently increased heart rate and cardiac index. A dose-dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriuresis increased 7-fold, 5-fold and 4-fold, respectively. Renal effects were not different between dosage groups. Compared with ANF(99-126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 micrograms kg-1, n = 6; ANF -1.8 +/- 0.5, URO: -5.5 +/- 1.1 mmHg, P less than 0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99-126) produced only a transient decrease of PAP. Similarly the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3 +/- 1.2 to 3.8 +/- 0.9 mmHg (P less than 0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficial effects in cardiovascular disease.

Background Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, long acting natriuretic peptide and kaliuretic peptide, and the kidney hormone urodilatin have anticancer effects in vitro. Materials and Methods These cardiac hormones and urodilatin were infused subcutaneously for 28 days with weekly fresh hormones since they lose biological effects at body temperature for more than a week at 0·3 nm kg−1 body weight in athymic mice bearing human small-cell lung carcinomas. Results Long acting natriuretic peptide, vessel dilator, kaliuretic peptide, atrial natriuretic peptide and urodilatin eliminated 86%, 71%, 57%, 43% (P

Background Mortality from renal-cell cancer remains a significant problem with an estimated 12 600 deaths in the United States in 2005 even with current treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide and kaliuretic peptide have significant anti-cancer effects in breast, pancreatic, prostate and colon adenocarcinomas. Materials and methods These four peptide hormones plus brain natriuretic peptide (BNP), C-natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney by a different post-translational processing of the atrial natriuretic peptide prohormone, were evaluated for their anti-cancer effects in renal carcinomas. Results Dose–response curves revealed a significant (P

The effects of a continuous i.v. infusion of urodilatin at a dose of 30 ng kg -1 min -1 were studied in a patient with congestive heart failure. After 30 min, urodilatin had induced a marked stimulation of plasma cyclic GMP concentrations. In parallel haematocrit increased. No significant diuresis and no change of invasive haemodynamics was observed. After 2 h the patient developed a profuse perspiration. Eighty minutes later he suffered from dizziness due to hypotension (blood pressure 80/40 mmHg) and a sudden bradycardia (50 bpm). Urodilatin was discontinued and symtoms were relieved by bed tilt and rapid infusion of isotonic saline solution. Mechanisms contributing to these adverse effects may be fluid extravasation to the third space and sympathoinhibitory effects known to occur with natriuretic peptide infusion

Urodilatin (ANF(95–126)) is an analogue of the atrial natriuretic factor (ANF(99–126)), which has been isolated from human urine. Recently we have shown in healthy volunteers, that intravenous bolus injections of synthetic urodilatin produce more pronounced reductions of pulmonary arterial pressure than ANF(99–126). To compare haemodynamic and renal effects of synthetic urodilatin with those of ANF(99–126) in congestive heart failure (CHF), 12 patients (66.3 ± 1.4 years) received either two high dose intravenous bolus injections of 4 μg kg-1 bw Urodilatin (URO) at a 30 min interval (n= 6) or the same doses of ANF(99–126)(n = 6). Prior to i.v. URO, no URO immunoreactivity was found in human plasma (specific RIA, no crossreactivity to ANF). Similar to ANF, the increase in diuresis (1.4 ± 0.7 to 3.7+1.6 ml min-1) and natriuresis (169 ±114 to 430 ± 197 μmol min-1) was moderate after URO in CHF. During the 90 min study period, mean plasma cyclic GMP levels increased much more after URO (by 53.4 ±15.1 nM) than after ANF (by 13.1 ± 30 nM; P= 0.04). In contrast to ANF, i.v. bolus injections of URO produced sustained haemodynamic effects in CHF lasting up to 90 min: The average (0–90 min) reduction of systemic vascular resistance was more pronounced after URO (- 578 ± 148) than after ANF (- 204 ± 65 dyn*s*cm-5, P= 0.04). Average increase of stroke volume index (URO: 9.5 ±1.9; ANF: 2.8 ±1.4 ml min-1 m-2; P= 0.02) and reduction of pulmonary capillary wedge pressure (URO: — 10.8 ± 2.1; ANF: - 3.9 ± 1.6 mmHg; P= 0.03)were more prominent after URO. These data indicate that urodilatin bolus injections produce sustained beneficial haemodynamic effects in patients with congestive heart failure, which are prolonged and more pronounced than after ANF. The larger increase in plasma cyclic GMP levels in CHF suggests that in the cardiovascular system of heart failure patients, URO may induce a more potent stimulation of guanylate cyclase coupled ANF receptors than ANF(99–126).